RESUMO
The presence of redundant copy number variants (CNVs) in groups of patients with neurological diseases suggests that these variants could have pathogenic effect. We have collected array comparative genomic hybridization (CGH) data of about 2,500 patients affected by neurocognitive disorders and we observed that CNVs in 2p16.3 locus were as frequent as those in 15q11.2, being both the most frequent unbalances in our cohort of patients. Focusing to 2p16.3 region, unbalances involving NRXN1 coding region have been already associated with neuropsychiatric disorders, although with incomplete penetrance, but little is known about CNVs located proximal to the gene, in the long noncoding RNA AK127244. We found that, in our cohort of patients with neuropsychiatric disorders, the frequency of CNVs involving AK127244 was comparable to that of NRXN1 gene. Patients carrying 2p16.3 unbalances shared some common clinical characteristics regardless NRXN1 and AK127244 CNVs localization, suggesting that the AK127244 long noncoding RNA could be involved in neurocognitive disease with the same effect of NRXN1 unbalances. AK127244 as well as NRXN1 unbalances seem to have a particular influence on language development, behavior or mood, according with the topographic correlation between NRXN1 expression and prefrontal cortex functions.
Assuntos
Cromossomos Humanos Par 2 , Transtornos Mentais/genética , RNA Longo não Codificante/genética , RNA não Traduzido/genética , Adolescente , Adulto , Proteínas de Ligação ao Cálcio , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/genética , Criança , Pré-Escolar , Estudos de Coortes , Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Transtornos Mentais/metabolismo , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão de Célula Nervosa , Fenótipo , RNA Longo não Codificante/metabolismo , RNA não Traduzido/metabolismoRESUMO
In this study, we sought to demonstrate that deficits in a specific motor activity, handwriting, are associated to Developmental Dyslexia. The linguistic and writing performance of children with Developmental Dyslexia, with and without handwriting problems (dysgraphia), were compared to that of children with Typical Development. The quantitative kinematic variables of handwriting were collected by means of a digitizing tablet. The results showed that all children with Developmental Dyslexia wrote more slowly than those with Typical Development. Contrary to typically developing children, they also varied more in the time taken to write the individual letters of a word and failed to comply with the principles of isochrony and homothety. Moreover, a series of correlations was found among reading, language measures and writing measures suggesting that the two abilities may be linked. We propose that the link between handwriting and reading/language deficits is mediated by rhythm, as both reading (which is grounded on language) and handwriting are ruled by principles of rhythmic organization.
Assuntos
Agrafia/fisiopatologia , Fenômenos Biomecânicos/fisiologia , Dislexia/fisiopatologia , Escrita Manual , Percepção do Tempo/fisiologia , Agrafia/diagnóstico , Criança , Computadores de Mão , Dislexia/diagnóstico , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Leitura , Percepção de Tamanho/fisiologiaRESUMO
We present the neuropsychological and linguistic follow-up of a girl with bilateral perisylvian polymicrogyria during 4 years of gestural and verbal speech therapy. Some researchers have suggested that children with bilateral perisylvian polymicrogyria mentally fail to reach the syntactic phase and do not acquire a productive morphology. This patient achieved a mean length of utterance in signs/gestures of 3.4, a syntactic phase of completion of the nuclear sentence and the use of morphological modifications. We discuss the link between gesture and language and formulate hypotheses on the role of gestural input on the reorganization of compensatory synaptic circuits.
Assuntos
Comunicação , Doenças do Nervo Facial/psicologia , Gestos , Deficiência Intelectual/psicologia , Idioma , Criança , Eletroencefalografia , Feminino , Seguimentos , Lateralidade Funcional/fisiologia , Humanos , Testes de Inteligência , Desenvolvimento da Linguagem , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Língua de Sinais , Síndrome , VocabulárioRESUMO
We assessed intelligence and receptive and expressive language skills in 6 children, ages 7 years 9 months to 12 years 4 months, with bilateral perisylvian polymicrogyria of variable extent and with dysarthria of different severity. In view of the recent findings of a close relationship between word and gesture, we also examined the communicative use of gesture. We found that mental retardation was related to the extent of cortical malformation; lexical comprehension, but not morphosyntactic comprehension, and verbal production were more compromised than expected from nonverbal intellectual abilities; lack of verbal language was not compensated by the use of referential gestures. Results are discussed suggesting that compromised verbal and gestural communication in bilateral perisylvian polymicrogyria are not due simply to mental retardation and/or dysarthria but also to dysfunction of Sylvian fissure areas concerned with the totality of language processing.
